basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18858803  33 EHRKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRVQ 95
Cdd:cd11459   1 EHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRQQ 63

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18858803  33 EHRKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRVQ 95
Cdd:cd11459   1 EHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRQQ 63

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 18858803    35 RKSSKPIMEKRRRARINESLGQLKTLILdalkkDSSRHSKLEKADILEMTVKHLRNLQ 92
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLP-----TLPPDKKLSKAEILRLAIEYIKHLQ 53

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 18858803     40 PIMEKRRRARINESLGQLKTLILDALKkdssrHSKLEKADILEMTVKHLRNLQRVQMS 97
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPK-----NKKLSKAEILRLAIEYIKSLQEELQK 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split HES-1, HES-4 and similar proteins; The family includes two bHLH-O transcriptional repressors, HES-1 and HES-4. HES-1, also termed Class B basic helix-loop-helix protein 39 (bHLHb39), or hairy homolog, or hairy-like protein (HL), plays an essential role in development of both compartment and boundary cells of the central nervous system. It regulates the maintenance of neural stem/progenitor cells by inhibiting proneural gene expression via Notch signaling. HES-4, also termed Class B basic helix-loop-helix protein 42 (bHLHb42), or bHLH factor Hes4, antagonizes the function of Twist-1 to regulate lineage commitment of bone marrow stromal/stem cells (BMSC). Epigenetic dysregulation of HES-4 is associated with striatal degeneration in postmortem Huntington brains. Both HES-1 and HES-4 are mammalian counterparts of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18858803  33 EHRKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRVQ 95
Cdd:cd11459   1 EHRKSSKPIMEKRRRARINESLSQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRQQ 63

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES) family; The HES family includes bHLH-O transcriptional regulators that are related to the Drosophila hairy and Enhancer-of-split (HES) proteins. They contain a basic helix-loop-helix (bHLH) domain with an invariant proline residue in its basic region, an orange domain in the central region and a conserved tetrapeptide motif, WRPW, at its C-terminal region. HES family proteins form heterodimers or homodimers via their HLH domain and bind DNA to repress gene transcription that play an essential role in development of both compartment and boundary cells of the central nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 18858803  42 MEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRVQ 95
Cdd:cd11410   1 MEKKRRARINKSLEQLKTLVLEALNKDNTRYSKLEKADILEMTVKYLKQLQRSK 54

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster enhancer of split mbeta protein (ESMB) and similar proteins; ESMB, also termed E(spl)mbeta, or HLH-mbeta, or split locus enhancer protein mA, is a bHLH-O transcriptional repressor of genes that require a bHLH protein for their transcription. It is involved in the neural-epidermal lineage decision during early neurogenesis. The family also includes Enhancer of split m7 protein (also known as E(spl)m7), which acts as a transcriptional repressor that participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18858803  32 SEHRKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQR 93
Cdd:cd19741   5 YQYRKVTKPLLERKRRARINKCLDELKDLMVEALATEAENVSKLEKADILELTVRHLKKLRR 66

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split 7 (HES-7) and similar proteins; HES-7, also termed Class B basic helix-loop-helix protein 37 (bHLHb37), or bHLH factor Hes7, is a bHLH-O transcriptional repressor that is expressed in an oscillatory manner and acts as a key regulator of the pace of the segmentation clock. It is regulated by the Notch and Fgf/Mapk pathways. HES-7 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858803  35 RKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRV 94
Cdd:cd11462   1 RKLLKPLVEKRRRDRINRSLEELRVLLLQNTQDEKLKNPKVEKAEILELTVQFLRNSSLS 60

basic helix-loop-helix-orange (bHLH-O) domain found in hairy and enhancer of split (HES)-related repressor protein (HERP) family; HERP (also called Hey/Hesr/HRT/CHF/gridlock) proteins corresponds to a family of bHLH-O transcriptional repressors that are related to the Drosophila hairy and Enhancer-of-split proteins and act as downstream effectors of Notch signaling. They contain a basic helix-loop-helix (bHLH) domain with an invariant glycine residue in its basic region, an orange domain in the central region and YXXW sequence motif at its C-terminal region. HERP proteins are involved in cardiovascular development and have roles in somitogenesis, myogenesis and gliogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18858803  35 RKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNLQ 92
Cdd:cd11407   1 RKKRRGIIEKRRRDRINNSLAELRRLVPTAFEKQGS--AKLEKAEILQMTVDHLKMLH 56

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-3 and similar proteins; HES-3, also termed Class B basic helix-loop-helix protein 43 (bHLHb43), or hairy and enhancer of split 3, is a bHLH-O transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. It regulates gene expression, cell growth, and insulin release. HES-3 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18858803  42 MEKRRRARINESLGQLKTLiLDALKKDSSRHSKLEKADILEMTVKHLRNLQ 92
Cdd:cd18933   1 MEKKRRARINVSLEQLKSL-LEKHYSNNIRKRKLEKADILELTVKYLRSLQ 50

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 18858803    35 RKSSKPIMEKRRRARINESLGQLKTLILdalkkDSSRHSKLEKADILEMTVKHLRNLQ 92
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLP-----TLPPDKKLSKAEILRLAIEYIKHLQ 53

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and similar proteins; HEY1, also termed cardiovascular helix-loop-helix factor 2 (CHF-2), or Class B basic helix-loop-helix protein 31 (bHLHb31), or HES-related repressor protein 1, or hairy and enhancer of split-related protein 1 (HESR-1), or hairy-related transcription factor 1 (HRT-1), is a bHLH-O transcriptional repressor that acts as an essential downstream effector of the Notch signaling pathway and may play a fundamental role in vascular development. HEY1 also participates several cancer-related pathways. It acts as a positive regulator of the tumor suppressor p53.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18858803  35 RKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNLQ 92
Cdd:cd19748   9 RKRRRGIIEKRRRDRINNSLSELRRLVPSAFEKQGS--AKLEKAEILQMTVDHLKMLH 64

basic helix-loop-helix-orange (bHLH-O) domain found in transcription factor HES-6 and similar proteins; HES-6, also termed Class B basic helix-loop-helix protein 41 (bHLHb41), or hairy and enhancer of split 6, or C-HAIRY1, is a bHLH-O transcription factor that is expressed in developing muscle and involved in angiogenesis, myogenesis, neural differentiation and neurogenesis. HES-6 antagonizes Notch signaling but is not regulated by Notch signaling. It is a transcription co-factor associated with stem cell characteristics in neural tissue. It may act as an inhibitor of Hes-1 during neuronal development and forms a heterodimer with HES-1 to prevent its association with transcriptional co-repressors. The overexpression of HES-6 has been reported in metastatic cancers of different origins. HES-6 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18858803  35 RKSSKPIMEKRRRARINESLGQLKTLIldalkKDSSRHSKLEKADILEMTVKHLRNLQR 93
Cdd:cd11460   3 RKARKPLVEKKRRARINESLQELRLIL-----ADAELQSKMENAEVLELTVKRVQGILR 56

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster Enhancer of split proteins, E(spl)m5, E(spl)m8 and similar proteins; The family includes two bHLH-O transcriptional repressors, E(spl)m5 and E(spl)m8, which participate in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. They bind DNA on N-box motifs, 5'-CACNAG-3'.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18858803  36 KSSKPIMEKRRRARINESLGQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNLQ 92
Cdd:cd18916   1 KSKKPMLERQRRARINKCLSELKTLVAECSGDDGC--LRMDKAEMLETAVAFMRQQQ 55

basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins; HEY2, also termed cardiovascular helix-loop-helix factor 1 (CHF-1), or Class B basic helix-loop-helix protein 32 (bHLHb32), or HES-related repressor protein 2, or hairy and enhancer of split-related protein 2 (HESR-2), or hairy-related transcription factor 2 (HRT-2), or protein gridlock homolog, is a bHLH-O transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. As a downstream effector of Notch signaling, HEY2 may be required for cardiovascular development. It also plays an important role in neurologic development, as well as in the progression of human cancers.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18858803  35 RKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNLQ 92
Cdd:cd18920  10 RKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQGS--AKLEKAEILQMTVDHLKMLQ 65

basic helix-loop-helix-orange (bHLH-O) domain found in differentially expressed in chondrocytes protein (DEC) family; The DEC family includes two bHLH-O transcriptional repressors, DEC1 and DEC2, which are widely expressed in both embryonic and adult tissues and have been implicated in apoptosis, cell proliferation, and circadian rhythms, as well as malignancy in various cancers. They mediate the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. They are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18858803  41 IMEKRRRARINESLGQLKTLILDALKKDSSRHskLEKADILEMTVKHLRNL 91
Cdd:cd11409  10 LIEKKRRDRINECIAQLKDLLPEHLKLTTLGH--LEKAVVLELTLKHLKAL 58

basic helix-loop-helix-orange (bHLH-O) domain found in Drosophila melanogaster protein clockwork orange (Cwo) and similar proteins; Cwo is a bHLH-O transcriptional regulator involved in the regulation of Drosophila circadian rhythms. It functions as both an activator and a repressor of clock gene expression.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18858803  38 SKPIMEKRRRARINESLGQLKTLILDA-LKKDSSRhskLEKADILEMTVKHLRNLQ 92
Cdd:cd11440   5 SHRIIEKRRRDRMNNCLADLSRLIPPTyLKKGRGR---IEKTEIIEMAIKHIKHLQ 57

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18858803  36 KSSKPIMEKRRRARINESLGQLKTLildaLKKDSSRhsKLEKADILEMTVKHLRNLQRV 94
Cdd:cd18908   3 ASSHSLKERLRRERIKSSCDQLRDL----LPYIKGR--KLDMASVLEMTVKYIRYIQER 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in USF/MITF family; The USF (upstream stimulatory factor)/MITF (microphthalmia-associated transcription factor) family includes two bHLHzip transcription factor subfamilies. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements. The MITF (also known as microphthalmia-TFE, or MiT) subfamily comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF subfamily proteins can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18858803  43 EKRRRARINESLGQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNLQR 93
Cdd:cd11387   6 ERRRRDNINEKIQELGSLVPPSRLETKD--LKPNKGSILSKAVEYIRELQN 54

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain family; bHLH-PAS domain has been found in a large group of bHLH transcription regulators that are involved in gene expression responding to environmental change and controlling aspects of neural development, including proteins from aryl hydrocarbon receptor nuclear translocator (ARNT) family, hypoxia-inducible factor (HIF) family, aryl hydrocarbon receptor (AhR) family, neuronal PAS domain-containing protein (NPAS) family, Circadian locomotor output cycles protein kaput (CLOCK)-like family, and single-minded (SIM) family. bHLH-PAS transcriptional regulatory factors have a bHLH DNA-binding domain followed by two PAS domains and a C-terminal activation or repression domain. bHLH-PAS family members can be divided into class I and class II based on their dimerization partner. bHLH-PAS class I factors include AhR, HIF and SIM. The best characterized bHLH-PAS Class II protein is the ubiquitous ARNT. Some members of bHLH-PAS family act as transcriptional coactivators (such as NCoA) that lack the ability to dimerize and bind DNA.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18858803  35 RKSSKPImEKRRRARINESLGQLKTLildaLKKDSSRHSKLEKADILEMTVKHLR 89
Cdd:cd11391   1 REKSREA-AKKRRDKENAEISELASL----LPLPPAVGSKLDKLSVLRLAVAYLR 50

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor E3 (TFE3) and similar proteins; TFE3, also termed Class E basic helix-loop-helix protein 33 (bHLHe33), is a bHLHzip transcription factor that is involved in B cell function. It specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Its efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18858803  34 HRKSSKPIMEKRRRARINESLGQLKTLIldalKKDSSRHSKLEKADILEMTVKHLRNLQRVQMSA 98
Cdd:cd18928  10 QKKDNHNLIERRRRFNINDRIKELGTLI----PKSTDPEMRWNKGTILKASVDYIRKLQKEQQRS 70

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the microphthalmia-associated transcription factor family (MITF) family; The MITF (also known as microphthalmia-TFE, or MiT) family is a small family that contain a basic helix loop helix domain associated with a leucine zipper (bHLHZip). The MITF family comprises four genes in mammals (MITF, TFE3, TFEB, and TFEC); each gene has different functions. MITF is involved in neural crest melanocytes development as well as the pigmented retinal epithelium. TFEB is required for vascularization of the mouse placenta. TFE3 is involved in B cell function. TFEC regulates gene expression in macrophages. The MITF family can form homodimers or heterodimers with each other but not with other bHLH or bHLHzip proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18858803  35 RKSSKPIMEKRRRARINESLGQLKTLildaLKKDSSRHSKLEKADILEMTVKHLRNLQRVQ 95
Cdd:cd11397   5 KKDNHNMIERRRRFNINDRIKELGTL----LPKSNDPDMRWNKGTILKASVDYIRKLQKEQ 61

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MLX-interacting protein (MLXIP), MLX-interacting protein-like (MLXIPL) and similar proteins; The family includes MLXIP and MLXIPL. MLXIP, also termed Class E basic helix-loop-helix protein 36 (bHLHe36), or transcriptional activator MondoA, is a bHLHZip transcriptional activator that binds DNA as a heterodimer with Mlx. It binds to the canonical E box sequence 5'-CACGTG-3' and plays a role in transcriptional activation of glycolytic target genes. MLXIP is most highly expressed in skeletal muscle and functions as an indirect glucose sensor, by sensing glucose 6-phosphate and shuttling between the nucleus and the cytoplasm. MLXIPL, also termed carbohydrate-responsive element-binding protein (ChREBP), or Class D basic helix-loop-helix protein 14 (bHLHd14), or MLX interactor, or WS basic-helix-loop-helix leucine zipper protein (WS-bHLH), or Williams-Beuren syndrome chromosomal region 14 protein (WBSCR14), is a bHLHZip transcriptional factor integral to the regulation of glycolysis and lipogenesis in the liver. It forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence 5'-CACGTG-3'.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18858803  33 EHRKSSKPIMEKRRRARINESLGQLKTLIlDALkkDSSRHSKLEKADILEMTVKHLRNLQR 93
Cdd:cd11405   1 EQRRLSHISAEQKRRFNIKSGFDTLQSLI-PSL--GQNPNQKVSKAAMLQKAAEYIKSLKR 58

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar proteins; The family includes several bHLH transcription factors from Arabidopsis thaliana, such as PIFs, ALC, PIL1, SPATULA, and UNE10. PIFs (PIF1, PIF3, PIF4, PIF5, PIF6 and PIF7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals. ALC, also termed AtbHLH73, or protein ALCATRAZ, or EN 98, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells. PIL1, also termed AtbHLH124, or protein phytochrome interacting factor 3-like 1, or EN 110, is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation. SPATULA, also termed AtbHLH24, or EN 99, plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them. UNE10, also termed AtbHLH16, or protein UNFERTILIZED EMBRYO SAC 10, or EN 99, is required during the fertilization of ovules by pollen.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18858803  43 EKRRRARINESLGQLKTLIldalkkdsSRHSKLEKADILEMTVKHLRNLQ-RVQM 96
Cdd:cd11445  10 ERRRRDRINEKMKALQELI--------PNCNKTDKASMLDEAIEYLKSLQlQVQM 56

basic helix-loop-helix (bHLH) domain found in the spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein (SOHLH) family and similar proteins; The SOHLH family includes two bHLH transcription factors, SOHLH1 and SOHLH2. They are specifically in spermatogonia and oocytes and essential for early spermatogonial and oocyte differentiation. The family also includes transcription factor-like 5 protein (TCFL5) and similar proteins. TCFL5, also termed Cha transcription factor, or HPV-16 E2-binding protein 1 (E2BP-1), is a bHLH transcription factor that plays a crucial role in spermatogenesis. It regulates cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 18858803  42 MEKRRRARINESLGQLKTLI--LDAlkkdssrhsKLEKADILEMTVKHLRNLQ 92
Cdd:cd19683   9 KERQRRERIKIACDQLRKLVpgCSR---------KTDKATVFEFTVAYIKFLR 52

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in upstream stimulatory factors, USF1, USF2 and similar proteins; Upstream stimulatory factor 1 and 2 (USF-1 and USF-2) are members of bHLHzip transcription factor family. USFs are ubiquitously expressed and key regulators of a wide number of gene regulation networks, including the stress and immune responses, cell cycle and proliferation, lipid and glucid metabolism. USFs recruit chromatin remodeling enzymes and interact with co-activators and the members of the transcription pre-initiation complex. USFs interact with high affinity to E-box regulatory elements.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 18858803  43 EKRRRARINESLGQLKTLILDALKKDSSrhSKLEKADILEMTVKHLRNLQRV 94
Cdd:cd11396   6 ERRRRDKINNWIVKLAKIVPDCEKDNSK--QGQSKGGILSKACDYIQELRSQ 55

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family and similar proteins; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box. The family also includes Saccharomyces cerevisiae transcription factor HMS1 (also termed high-copy MEP suppressor protein 1) and serine-rich protein TYE7. HMS1 is a putative bHLHzip transcription factor involved in exit from mitosis and pseudohyphal differentiation. TYE7, also termed basic-helix-loop-helix protein SGC1, is a putative bHLHzip transcription activator required for Ty1-mediated glycolytic gene expression. TYE7 N-terminal is extremely rich in serine residues. It binds DNA on E-box motifs, 5'-CANNTG-3'. TYE7 is not essential for growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858803  34 HRKsskpiMEKRRRARINESLGQLKTLI----------LDALKKDSSRHSKLEKADILEMTVKHLRNLQrvQMSAALSAD 103
Cdd:cd11395   7 HNA-----IEKRYRSNLNTKIERLRDAIpslrspegksDDGGLGGLAPTTKLSKATILTKAIEYIRHLE--QENERLEEE 79

                ....*...
gi 18858803 104 TNVLSKYR 111
Cdd:cd11395  80 NEELRQQV 87

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae phosphate system positive regulatory protein PHO4 and similar proteins; PHO4 is a transcriptional activator that regulates the expression of repressible phosphatase under phosphate starvation conditions in Saccharomyces cerevisiae. The PHO4 protein has four functional domains with the bHLH domain at its carboxyl-terminal region. It regulates transcription by binding to promoter of the genes as a homodimer.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18858803  43 EKRRRARINESLGQLKTLI-----LDALKKDSSRHSKLE-----------KADILEMTVKHLRNLQR 93
Cdd:cd11392  10 ERGRRDRLNAALKELASLMpaefvEGKMGADGSASDSNDkekaaasaagsKAATVEMAIDYIKHLQK 76

basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in Drosophila melanogaster protein cycle and similar proteins; Protein cycle, also termed brain and muscle ARNT-like 1 (BMAL1), or MOP3, is a putative bHLH-PAS transcription factor involved in the generation of biological rhythms in Drosophila. It activates cycling transcription of Period (PER) and Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their promoters.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18858803  42 MEKRRRARINESLGQLKTLIldALKKDSSRhsKLEKADILEMTVKHLRNLQ 92
Cdd:cd19726   8 IEKRRRDKMNTYITELSSMI--PMCNAMSR--KLDKLTVLRMAVQHMKTLR 54

basic helix-loop-helix (bHLH) domain found in Saccharomyces cerevisiae protein INO2 and similar proteins; INO2 is a positive regulatory factor required for depression of the co-regulated phospholipid biosynthetic enzymes in Saccharomyces cerevisiae. It is also involved in the expression of ITR1.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 18858803  42 MEKRRRARINESLGQLKTLILDALKKDSSRhskLEKADILEMTVKHLRNLQR 93
Cdd:cd11388  10 AEKKRRNQIKKGFEDLINLINYPRNNNEKR---ISKSELLNKAVDDIRGLLK 58